Novo Nordisk's IL-6 drug flunks two more heart trials

Novo Nordisk has opted to discontinue two late-stage trials of IL-6 inhibitor ziltivekimab in heart failure, after an interim look at the data suggested they would be unlikely to show a positive result.

The revelation – first reported by Endpoints – affects the placebo-controlled HERMES and ATHENA trials of ziltivekimab in patients with heart failure and inflammation, and comes after Novo Nordisk reported disappointing top-line results from the ZEUS trial in August.

It is a setback for the Danish drugmaker, which has been trying to diversify its pipeline beyond its core areas of diabetes, obesity, and rare diseases.

HERMES and ATHENA were hoping to show that dampening down the inflammatory response in heart failure patients with preserved or mildly reduced ejection fraction would improve outcomes like time to first cardiovascular death, heart failure hospitalisation, urgent heart failure visits, and quality of life. ZEUS, meanwhile, was run in patients with atherosclerotic cardiovascular disease (ASCVD) compounded by chronic kidney disease (CKD) and inflammation.

The news means that Novo Nordisk has only one remaining shot on goal with ziltivekimab in the form of the ARTEMIS trial, which is putting the drug through its paces as an acute treatment in the post-myocardial infarction setting, with results due next year.

It also increases the pressure on Novo Nordisk to carry out licensing deals and/or acquisitions to bolster its pipeline outside obesity and diabetes, which has been driving growth in recent years but where it is facing increasing pressure from rival Eli Lilly.

Novo Nordisk acquired ziltivekimab as part of its $725 million takeover of AstraZeneca spin-out Corvidia Therapeutics in 2020.

Data backs GLP-1 agonist semaglutide in children

Returning to its main franchise of GLP-1 agonist therapies, Novo Nordisk reported better news this morning from the STEP Young trial of semaglutide in children aged 6 to under 12 years old with class II or III severe obesity.

The trial met its primary endpoint, with a weekly subcutaneous injection of semaglutide helping 40% of children reduce their BMI below the threshold for obesity at 68 weeks, compared to 0% of the placebo group, with a safety profile consistent with older patients.

The data comes as researchers at NYU Langone Health in the US have published a study in the journal Paediatrics showing a 300-fold increase in prescribing of GLP-1 agonists to children under 12 between 2019 and 2026, although rates of prescribing remained low at less than 1%.

Around one in five children in the US are living with obesity, meaning their BMI is above the 95th percentile for children of similar age and sex, without having diabetes. Children living with obesity experience cardiovascular disease risk factors, alongside depression, eating disorders, and bullying, with studies showing that their quality of life is comparable to children undergoing cancer treatment.